RESUMO
We have previously shown that the probiotic Bifidobacterium breve strain Bif195 alleviates mucosal injury including ulcer formation in the upper intestine induced by non-steroid anti-inflammatory drugs (NSAIDs). Here, we report additional safety use of Bif195 in 126 healthy humans undergoing an exercise-induced intestinal permeability challenge in a double-blinded, placebo-controlled randomised 6-week intervention trial. Intestinal permeability was assessed by urinary lactulose/rhamnose (L/R) ratio. L/R ratio, plasma intestinal fatty acid binding protein (I-FABP) and gastrointestinal symptom rating scale (GSRS) questionnaire were measured resting and after a 1 h treadmill challenge, prior to and at the end of the intervention. To be able to compare the equivalence of resting state at baseline, of this cohort of well-trained subjects, to non-trained subjects, a cohort of 63 healthy and non-trained subjects (<2 h/week of endurance sports) was included. Study subjects (well-trained) were 35.7% women with a mean age and body mass index (in kg/m2) of 35.0 years and 24.8, respectively. There were no differences between the Bif195 and placebo groups in effects on L/R ratio, I-FABP and GSRS questionnaire score. In addition, there were no differences between Bif195 and placebo in number of adverse events and change in cytokines, liver or kidney biomarkers. The exercise model successfully induced intestinal permeability by statistically significantly increasing L/R ratio by ~100% (P<0.0001) and cytokines after the exercise challenge. No significant difference was found between well-trained and non-trained subjects in baseline resting L/R ratio. In conclusion, the reported cytoprotective effects of Bif195 are unlikely to be primarily related to small bowel permeability, and the safety of Bif195 in individuals with increased permeability is supported by the present data. ClinicalTrials.gov: NCT03027583.
Assuntos
Bifidobacterium breve , Probióticos , Adulto , Citocinas , Método Duplo-Cego , Feminino , Humanos , Intestinos , Lactulose , Masculino , PermeabilidadeRESUMO
Randomised controlled clinical trials (RCTs) offer a unique opportunity to obtain controlled efficacy and safety data to support clinical decisions. However, most RCT reporting has a stronger focus on efficacy rather than safety. This study aimed to identify the safety profile of both probiotic and drug interventions in irritable bowel syndrome (IBS). In connection to this paper, an accompanying paper was published in which a meta-analysis was conducted to evaluate the efficacy of probiotic interventions compared to that of drug interventions in IBS. Together, these two studies provide a first assessment regarding the feasibility to determine a burden to benefit ratio for both probiotic and drug interventions in IBS. RCTs including participants (>18 years old) with IBS and comparing probiotic or drugs interventions with control groups were identified by a systematic search of MEDLINE (January 2015 - Jan 2021). Reported safety profiles in drug studies were completer and more detailed as compared with studies on probiotics. Several inconsistencies in safety reporting were identified between and within drug and probiotic studies, such as: didn't report on safety; only reported adverse reactions (ARs) or adverse events (AEs) with a certain severity; didn't report the total number of AEs; didn't split in the control- or experimental arm; didn't specify AEs; and used different thresholds for 'common' AEs. Hence, it is difficult to compare safety data from drug and probiotic RCTs across and between different studies. On the current approaches to safety reporting, we could not establish an unambiguous safety profile for neither probiotic and drug interventions in IBS. These shortcomings hamper a critical comparison of the burden to benefit ratio for IBS intervention.
Assuntos
Síndrome do Intestino Irritável , Probióticos , Adolescente , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Probióticos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Clinical decisions made by health professionals to recommend either drug or probiotic interventions for irritable bowel syndrome (IBS) should be supported by proper knowledge of the efficacy rates of both types of interventions. In this article, we performed a systematic review and meta-analysis to examine the efficacy of both probiotic- and drug interventions in IBS. Medline was searched between January 2015 - January 2021. Randomised controlled trials (RCT) recruiting participants > 18 years old with IBS and examining the effect of probiotics or drugs were eligible for inclusion. The data of the primary outcome, i.e. the persistence of IBS symptoms (dichotomous symptom data), were pooled to obtain a relative risk (RR), with a 95% confidence interval (CI). Secondary outcomes, abdominal pain- and bloating scores (continuous data), were pooled using a standardised mean difference with a 95% CI. The search identified 269 citations of which 32 RCTs were eligible. Our meta-analysis indicated that both probiotic and drug interventions are able to improve the persistence of IBS symptoms (RR 0.60 [0.51; 0.92] versus 0.87 [0.81; 0.92], respectively) and abdominal pain scores (standardised mean difference (SMD) -0.35 [-0.56; -0.14] versus -0.10 [-0.20; 0.00], respectively). However, determining the overall efficacy of both intervention types is inherently complex and such results should be interpreted with care, due to the large diversity of probiotic- and drug types and doses, which is also complicated by variety in IBS subtypes. Hence, as a first step, more large scale randomised double blind placebo-controlled trials focussing on a specific IBS subtype targeted with specific probiotic strains or specific pharmaceutical modalities should be executed, enabling a more proper comparison between trials.
Assuntos
Síndrome do Intestino Irritável , Probióticos , Dor Abdominal/tratamento farmacológico , Adolescente , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/tratamento farmacológico , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.
Assuntos
Bactérias/metabolismo , Transplante de Microbiota Fecal , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/terapia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Fezes/química , Fezes/microbiologia , Microbioma Gastrointestinal , Humanos , Síndrome do Intestino Irritável/microbiologia , Filogenia , Resultado do TratamentoRESUMO
Nutritional intervention studies, like those with pre- and probiotics, are often hampered by low effect sizes, reducing the power to demonstrate potential efficacy. Here, we perform computer simulations of a hypothetical clinical trial using such an intervention in order to elucidate determining factors that can be influenced in order to optimise the statistical power. Our simulations demonstrate that steering the study population towards a low intraindividual variation dramatically improves statistical power. A more than 10-fold decrease of number-to-treat could be reached. Also, a careful balancing between the number of subjects and measurements per subject, in combination with possible stratification of the subjects into responders and non-responders, based on inherent intraindividual variation, improves the likelihood to reach statistically significant results. Our results also show that traditional dogmas, with respect to clinical trials, i.e. aiming at low interindividual variation and a high number (n) of study participants, should be re-evaluated in favour of reducing intraindividual variation. This reduction in intraindividual variation could be achieved by maintaining a steady lifestyle, including dietary habits among others, within the timeframe of the intervention study.
Assuntos
Variação Biológica Individual , Ensaios Clínicos como Assunto/métodos , Ciências da Nutrição , Prebióticos , Probióticos/uso terapêutico , Projetos de Pesquisa , Simulação por Computador , Humanos , Números Necessários para TratarRESUMO
Gastrointestinal problems are common in elderly and often associated with psychological distress and increased levels of corticotrophin-releasing hormone, a hormone known to cause mast cell (MC) degranulation and perturbed intestinal barrier function. We investigated if dietary fibres (non-digestible polysaccharides [NPS]) could attenuate MC-induced colonic hyperpermeability in elderly with gastrointestinal (GI) symptoms. Colonic biopsies from elderly with diarrhoea and/or constipation (n = 18) and healthy controls (n = 19) were mounted in Ussing chambers and pre-stimulated with a yeast-derived beta (ß)-glucan (0.5 mg/ml) or wheat-derived arabinoxylan (0.1 mg/ml) before the addition of the MC-degranulator Compound (C) 48/80 (10 ng/ml). Permeability markers were compared pre and post exposure to C48/80 in both groups and revealed higher baseline permeability in elderly with GI symptoms. ß-glucan significantly attenuated C48/80-induced hyperpermeability in elderly with GI symptoms but not in healthy controls. Arabinoxylan reduced MC-induced paracellular and transcellular hyperpermeability across the colonic mucosa of healthy controls, but did only attenuate transcellular permeability in elderly with GI symptoms. Our novel findings indicate that NPS affect the intestinal barrier differently depending on the presence of GI symptoms and could be important in the treatment of moderate constipation and/or diarrhoea in elderly.
Assuntos
Colo/metabolismo , Constipação Intestinal/metabolismo , Diarreia/metabolismo , Fibras na Dieta/farmacologia , Absorção Intestinal , Xilanos , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Biópsia , Degranulação Celular/efeitos dos fármacos , Colo/patologia , Colo/fisiopatologia , Constipação Intestinal/patologia , Constipação Intestinal/fisiopatologia , Diarreia/patologia , Diarreia/fisiopatologia , Feminino , Humanos , Masculino , Mastócitos/metabolismo , Mastócitos/patologia , Permeabilidade/efeitos dos fármacos , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia , Estresse Psicológico/fisiopatologia , Xilanos/farmacocinética , Xilanos/farmacologiaRESUMO
BACKGROUND: Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication. AIM: To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT. METHODS: Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors. RESULTS: Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings. CONCLUSIONS: Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.
Assuntos
Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Doenças Inflamatórias Intestinais/terapia , Síndrome do Intestino Irritável/terapia , Síndrome Metabólica/terapia , Animais , Fezes/microbiologia , Microbioma Gastrointestinal , HumanosRESUMO
BACKGROUND: The faecal-associated microbiota is commonly seen as a surrogate of the mucosal-associated microbiota. However, previous studies indicate that they are different. Furthermore, analyses of the mucosal microbiota are commonly done after standard bowel cleansing, affecting the microbial composition. AIM: To compare the mucosal-associated microbiota, obtained from unprepared colon, with faecal-associated microbiota in healthy subjects and irritable bowel syndrome (IBS) patients. METHODS: Faecal and mucosal biopsies were obtained from 33 IBS patients and 16 healthy controls. Of IBS patients, 49% belonged to the diarrhoea-predominant subgroup and 80% suffered from IBS symptoms during at least 5 years. Biopsies were collected from unprepared sigmoid colon and faecal samples a day before colonoscopy. Microbiota analyses were performed with a phylogenetic microarray and redundancy discriminant analysis. RESULTS: The composition of the mucosal- and the faecal-associated microbiota in unprepared sigmoid colon differs significantly (P = 0.002). Clinical characteristics of IBS did not correlate with this difference. Bacteroidetes dominate the mucosal-associated microbiota. Firmicutes, Actinobacteria and Proteobacteria dominate the faecal-associated microbiota. Healthy subjects had a significantly higher (P < 0.005) abundance (1.9%) of the bacterial group uncultured Clostridiales I in the mucosal-associated microbiota than IBS patients (0.3%). Bacterial diversity was higher in faecal- compared with mucosal-associated microbiota in IBS patients (P < 0.005). No differences were found in healthy subjects. CONCLUSIONS: Differences in the mucosal-associated microbiota between healthy individuals and IBS patients are minimal (one bacterial group) compared to differences in the faecal microbiota of both groups (53 bacterial groups). Microbial aberrations characterising IBS are more pronounced in the faeces than in the mucosa.
Assuntos
Diarreia/microbiologia , Fezes/microbiologia , Síndrome do Intestino Irritável/microbiologia , Microbiota , Adulto , Biópsia , Colonoscopia , Feminino , Humanos , Intestinos/microbiologia , Síndrome do Intestino Irritável/diagnóstico , Masculino , Pessoa de Meia-Idade , Mucosa/microbiologia , Filogenia , Adulto JovemRESUMO
This study aimed to systematically evaluate safety of probiotics and synbiotics in children ageing 0-18 years. This study is the third and final part in a safety trilogy and an update is provided using the most recent available clinical data (2008-2013) by means of the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 74 clinical studies indicated that probiotic and/or synbiotic administration in children is safe with regard to the specific evaluated strains, dosages and duration. The population of children include healthy, immune compromised and obese subjects, as well as subjects with intestinal disorders, infections and inflammatory disorders. This study revealed no major safety concerns, as the adverse events (AEs) were unrelated, or not suspected to be related, to the probiotic or synbiotic product. In general the study products were well tolerated. Overall, AEs occurred more frequent in the control arm compared to children receiving probiotics and/or synbiotics. Furthermore, the results indicate inadequate reporting and classification of AEs in the majority of the studies. In addition, generalizability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes.
Assuntos
Probióticos/administração & dosagem , Probióticos/efeitos adversos , Simbióticos/administração & dosagem , Simbióticos/efeitos adversos , Adolescente , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Lactente , Recém-NascidoRESUMO
BACKGROUND: Psychosocial stress may influence peptic ulcer disease (PUD) risk, but it can be difficult to identify reliably whether stressful exposures pre-dated disease. The association of stress resilience (susceptibility to stress) with subsequent PUD risk has been incompletely investigated. AIM: To assess if stress resilience in adolescence is associated with subsequent PUD risk. METHODS: The participants comprised of 233 093 men resident in Sweden, born 1952-1956 and assessed for compulsory military conscription during 1969-1976, with data provided by national Swedish registers. Stress resilience was evaluated through semi-structured interviews by a certified psychologist. Cox regression assessed the association between stress resilience in adolescence and the risk of PUD from 1985 to 2009, between ages 28 and 57 years, with adjustment for parental socioeconomic index, household crowding and number of siblings in childhood, as well as cognitive function and erythrocyte sedimentation rate in adolescence. RESULTS: In total, 2259 first PUD diagnoses were identified. Lower stress resilience in adolescence is associated with a higher risk of PUD in subsequent adulthood: compared with high resilience, the adjusted hazard ratios (and 95% CI) are 1.84 (1.61-2.10) and 1.23 (1.09-1.38) for low and moderate stress resilience, respectively. CONCLUSION: Stress may be implicated in the aetiology of PUD and low stress resilience is a marker of risk.
Assuntos
Úlcera Péptica/epidemiologia , Estresse Psicológico/complicações , Adolescente , Adulto , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/etiologia , Estudos Prospectivos , Risco , Estresse Psicológico/epidemiologia , Suécia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: A subset of irritable bowel syndrome (IBS) patients, denoted post-infectious IBS (PI-IBS), develop symptoms after an enteric infection. Bacterial dysbiosis and mucosal inflammation have been proposed to be involved in the pathophysiology of this entity. AIM: To characterise the mucosal and faecal microbiota in PI-IBS, general IBS and healthy controls, and to investigate associations between the microbiota and the mucosal immune system. METHODS: Mucosal biopsies and faeces were collected from 13 PI-IBS patients, 19 general IBS patients and 16 healthy controls. Global bacterial composition was determined by generating 16S rRNA amplicons that were examined by phylogenetic microarray hybridisation, principal component and redundancy analysis. We correlated previously reported lymphocyte proportions with the microbiota. RESULTS: Faecal microbiota composition of PI-IBS patients differed significantly from both general IBS patients and healthy controls (P < 0.02). Both mucosal (P < 0.01) and faecal (P = 0.05) microbial diversity were reduced in PI-IBS compared to healthy controls. In the intraepithelial lymphocytes the previously published proportion of CD8(+) CD45RA(+) was negatively correlated with mucosal microbial diversity (P < 0.005). The previously published number of lamina propria lymphocytes was negatively correlated with mucosal microbial diversity (P < 0.05). Faecal microbial diversity was significantly negatively correlated with the Hospital Anxiety and Depression scale (P < 0.05). CONCLUSIONS: We present data that distinguishes the intestinal microbiota of PI-IBS patients from that of both general IBS patients and HC. The microbial composition is significantly associated with the HADs score and alterations in lymphocyte subsets proportions.
Assuntos
Fezes/microbiologia , Mucosa Intestinal/microbiologia , Síndrome do Intestino Irritável/microbiologia , Adulto , Índice de Massa Corporal , Feminino , Gastrite/complicações , Humanos , Mucosa Intestinal/imunologia , Intestinos/patologia , Síndrome do Intestino Irritável/etiologia , Síndrome do Intestino Irritável/imunologia , Subpopulações de Linfócitos , Masculino , Microbiota/imunologia , Pessoa de Meia-Idade , Fenótipo , RNA Ribossômico 16SRESUMO
This study aimed to systematically evaluate safety of probiotics and synbiotics in immune compromised adults (≥18 years). Safety was analysed using the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification, thereby providing an update on previous reports using the most recent available clinical data (2008-2013). Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 57 clinical studies indicates that probiotic and/or synbiotic administration in immune compromised adults is safe with regard to the current evaluated probiotic strains, dosages and duration. Individuals were considered immune compromised if HIV-infected, critically ill, underwent surgery or had an organ- or an autoimmune disease. There were no major safety concerns in the study, as none of the serious adverse events (AE)s were related, or suspected to be related, to the probiotic or synbiotic product and the study products were well tolerated. Overall, AEs occurred less frequent in immune compromised subjects receiving probiotics and/or synbiotics compared to the control group. In addition, the results demonstrated a flaw in precise reporting and classification of AE in most studies. Furthermore, generalisability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes. We argue that standardised reporting on adverse events (CTCAE) in 'food' studies should be obligatory, thereby improving reliability of data and re-enforcing the safety profile of probiotics.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hospedeiro Imunocomprometido , Probióticos/administração & dosagem , Probióticos/efeitos adversos , Simbióticos/efeitos adversos , Adulto , Ensaios Clínicos como Assunto , HumanosRESUMO
The intestinal microbiota forms a complex ecosystem that is in close contact with its host and has an important impact on health. An increasing number of disorders are associated with disturbances in this ecosystem. Also patients suffering from irritable bowel syndrome (IBS) show an altered composition of their gut microbiota. IBS is a multifactorial chronic disorder characterised by various abdominal complaints and a worldwide prevalence of 10-20%. Even though its aetiology and pathophysiology are complex and not well understood, it is widely accepted that aberrations along the microbe-gut-brain axis are involved. In this review, it will be discussed how exogenous factors, e.g. antibiotics, can cause disbalance in the intestinal microbiota and thereby contribute to the development of IBS. In addition, several new IBS treatment options that aim at re-establishing a healthy, beneficial ecosystem will be described. These include antibiotics, probiotics, prebiotics and faecal transplantation.
Assuntos
Mucosa Intestinal/microbiologia , Síndrome do Intestino Irritável/microbiologia , Microbiota/efeitos dos fármacos , Microbiota/imunologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Fezes/microbiologia , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/patologia , Prebióticos , Probióticos/uso terapêutico , SimbióticosRESUMO
In this study, we systematically evaluated safety aspects in clinical trials with probiotics and synbiotics in young infants (0-2 years of age). This study is an update of earlier reports and covers the recent literature from 2008-2013. The safety evaluation is performed along the Common Terminology Clinical Adverse Events (CTCAE) version 4.0 scale, hereby also providing guidance for future studies. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. The results show a deficiency in the precise reporting and classification of adverse events in most studies. Analysis of 57 clinical trials with probiotics and synbiotics in combination with eight follow-up studies indicate that probiotic administration to infants between 0 and 24 months is safe with regard to the evaluated strains in infants with a particular health status or susceptibility. Most adverse events and serious adverse events were considered unrelated to the study product, and there were no major safety concerns. Almost all studies concluded that none of the adverse effects were related to the study product; the study products are generally well tolerated. Finally, inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes, greatly limit the generalizability of conclusions and argue convincingly for obligatory and standardised behaviour on adverse events (CTCAE) reporting in 'food' studies.
Assuntos
Trato Gastrointestinal/microbiologia , Probióticos/efeitos adversos , Probióticos/uso terapêutico , Simbióticos/efeitos adversos , Bifidobacterium , Disbiose/terapia , Inocuidade dos Alimentos , Humanos , Lactente , Recém-Nascido , LactobacillusRESUMO
Recent studies suggested that manipulation of the composition of the microbial ecosystem in the gut might be a novel approach in the treatment of obesity. Such treatment might consist of altering the composition of the microbial communities of an obese individual by administration of beneficial microorganisms, commonly known as probiotics. Here, we intend to contribute to the developmental process of probiotic treatment of human obesity. The aim is to review the evidence regarding the potential effect of probiotic strains on reduction of weight and body fat. A literature study was conducted focusing on clinical trials that examined the effect of specific microorganisms on body weight control. Analysis of the eligible articles pointed out that Lactobacillus gasseri SBT 2055, Lactobacillus rhamnosus ATCC 53103, and the combination of L. rhamnosus ATCC 53102 and Bifidobacterium lactis Bb12 may reduce adiposity, body weight, and weight gain. This suggests that these microbial strains can be applied in the treatment of obesity. Furthermore, short chain fatty acid production and low grade inflammation were found as the underlying mechanisms of action that influence metabolism and affect body weight. These findings might contribute to the development of probiotic treatment of obesity. Further research should be directed to the most effective combination and dosage rate of probiotic microorganisms.
Assuntos
Ácidos Graxos Voláteis/biossíntese , Trato Gastrointestinal/microbiologia , Inflamação/microbiologia , Obesidade/terapia , Probióticos/uso terapêutico , Tecido Adiposo/microbiologia , Adiposidade , Bifidobacterium/metabolismo , Peso Corporal , Humanos , Inflamação/imunologia , Lactobacillus/metabolismo , Microbiota , Redução de PesoRESUMO
BACKGROUND: Barostat methodology is widely used for assessing visceral perception. Different barostat protocols are described with respect to the measurement of rectal compliance and visceral perception. The choice of protocols affects the duration, which is normally 60-90 min, and accuracy of the procedure. This study aimed to shorten the procedure by using the semi-random distension protocol for both compliance and visceral perception measurement and a correction based on rectal capacity (RC) instead of minimal distension pressure (MDP). METHODS: Twelve irritable bowel syndrome (IBS) patients (7 females) and 11 healthy controls (8 females) underwent a barostat procedure. Compliance was determined during both a staircase distension and a semi-random protocol. Visceral perception data were compared as a function of pressure or relative volume, corrected for MDP or RC, respectively. RESULTS: Compliance measurement using the semi-random protocol instead of the staircase distension protocol resulted in an overestimation in healthy volunteers, but not in IBS patients. The overall conclusion that IBS patients had a lower compliance compared to controls was not different between protocols. Data presentation of the visceral perception scores as a function of corrected volume instead of pressures corrected for MDP did not alter the conclusion that sensation scores in IBS patients were higher as compared to healthy controls. CONCLUSIONS: This study showed that barostat procedures may be shortened by approximately 20 min, without losing the ability to discriminate between healthy controls and IBS patients. A correction for RC instead of MDP may improve the accuracy of the procedure.
Assuntos
Dilatação/métodos , Motilidade Gastrointestinal/fisiologia , Síndrome do Intestino Irritável/fisiopatologia , Reto/fisiopatologia , Adulto , Estudos de Casos e Controles , Protocolos Clínicos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Pressão , Fatores de TempoRESUMO
OBJECTIVE: Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD. METHODS: 12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years). RESULTS: In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C. CONCLUSIONS: The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.
Assuntos
Nível de Alerta/fisiologia , Emoções/fisiologia , Síndrome do Intestino Irritável/fisiopatologia , Triptofano/deficiência , Adulto , Tonsila do Cerebelo/fisiopatologia , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Dilatação , Métodos Epidemiológicos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Estimulação Física/métodos , Pressão , Reto/fisiopatologia , Limiar Sensorial/fisiologia , Adulto JovemRESUMO
Growth hormone (GH), a hormone originating from the anterior pituitary gland, is an important regulator of metabolism and body composition. Low GH secretion is associated with features of the metabolic syndrome, in particular increased visceral body fat and decreased lean body mass. It has been shown that GH release can be promoted by ingestion of protein, in particular gelatin protein. The question remains; is the GH-promoting effect of gelatin protein also present in a population with blunted GH response, such as visceral obesity? 8 lean women (age: 23+/-3 years, BMI: 21.6+/-2.0 kg/m (2)) and 8 visceral obese women (age: 28+/-7 years, BMI: 33.8+/-5.5 kg/m (2)) were compared with regard to their 5-h GH response after oral ingestion of gelatin protein (0.6 g protein per kg bodyweight), placebo (water), or injection of growth hormone releasing hormone (GHRH) (1 mu/kg body weight), in a randomized crossover design. GH response after placebo, gelatin protein, or GHRH was higher in lean subjects than in visceral obese subjects (p<0.05). Ingestion of gelatin protein increased GH response compared with placebo in both visceral obese (182.1+/-81.6 microg/l.5 h vs. 28.4+/-29.8 microg/l.5 h) and lean (631.7+/-144.2 microg/l.5 h vs. 241.0+/-196.8 microg/l.5 h) subjects (p<0.05). GH response after ingestion of gelatin protein in visceral obese did not differ from that in lean, placebo-treated subjects (p=0.45). GH concentrations after GHRH injection correlated significantly with GH concentrations after gelatin ingestion (AUC; r=0.71, p<0.01, Peak; r=0.81, p<0.01). Further research is needed to investigate if gelatin protein is able to improve metabolic abnormalities in hyposomatotropism in the long term or to investigate the relevance of protein as diagnostic tool in hyposomatotropism.
Assuntos
Comportamento Alimentar/efeitos dos fármacos , Gelatina/administração & dosagem , Gelatina/farmacologia , Hormônio do Crescimento Humano/sangue , Obesidade/sangue , Vísceras/metabolismo , Vísceras/patologia , Adulto , Feminino , Hormônio Liberador de Hormônio do Crescimento/administração & dosagem , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Humanos , Injeções Intravenosas , Obesidade/metabolismo , Vísceras/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVES: Age-related hearing loss is a common social and health problem in the older adult population. Up until now, very little scientific attention has been given to the potential role of fatty acids in age-related hearing loss. In this study we investigated whether plasma very long-chain n-3 polyunsaturated fatty acids (PUFAs) are associated with age-related hearing loss over three years. DESIGN: Cross-sectional and 3-year longitudinal analyses. SETTING: Wageningen, the Netherlands. PARTICIPANTS: 720 men and postmenopausal women (50-70 years of age) without middle ear dysfunction or unilateral hearing loss. MEASUREMENTS: Fatty acid proportions were measured in plasma cholesteryl esters. Hearing thresholds (in decibels, dB) at baseline and after three years were measured with pure-tone audiometry. Hearing loss was calculated as the increase in mean hearing thresholds in the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies over three years. RESULTS: Subjects in the highest quartile of plasma very long-chain n-3 PUFA had less hearing loss in the low frequencies over three years than subjects in the lowest quartile (p < 0.01, ANCOVA, difference in mean adjusted hearing thresholds= -1.2 dB). There were no significant differences between the quartiles of plasma very long-chain n-3 PUFA in hearing loss in the high frequencies (p=0.49, ANCOVA). These associations are adjusted for baseline mean hearing thresholds, age, sex, level of education and alcohol consumption. CONCLUSION: This study is the first to show an inverse association between plasma very long-chain n-3 PUFAs and age-related hearing loss. These results are encouraging, but require confirmation from future studies.
Assuntos
Envelhecimento/fisiologia , Limiar Auditivo/fisiologia , Ácidos Graxos Ômega-3/sangue , Presbiacusia/sangue , Idoso , Audiometria , Estudos Transversais , Ácidos Graxos Ômega-3/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Presbiacusia/etiologiaRESUMO
Fermentation of dietary fibres by colonic microbes leads to the production of short chain fatty acids (mainly propionate, butyrate and acetate), which are utilized by the colonic mucosa. Previous studies showed positive effects of butyrate on parameters of oxidative stress, inflammation and apoptosis. Recent studies in rats, however, showed that butyrate increased visceral sensitivity. The aim of this study was to determine the effects of physiologically relevant concentrations of butyrate on visceral perception in healthy human subjects. Eleven healthy volunteers participated in this randomized double-blind, placebo controlled cross-over study. The study consisted of three periods of 1 week each, in which the volunteers daily self-administered rectal enemas containing 100, 50 mmol L(-1) butyrate, or placebo (saline) prior to sleeping. A rectal barostat measurement was performed at the start and the end of each test period for the measurement of pain, urge and discomfort. Butyrate treatment resulted in a dose-dependent reduction of pain, urge and discomfort throughout the entire pressure range of the protocol. At a pressure of 4 mmHg, 50 and 100 mmol L(-1) butyrate concentrations resulted in a 23.9% and 42.1% reduction of pain scores, respectively, and the discomfort scores decreased by 44.2% and 69.0% respectively. At a pressure of 67 mmHg, 50 and 100 mmol L(-1) of butyrate decreased the pain scores by 23.8% and 42%, respectively, and discomfort scores 1.9% and 5.2% respectively. Colonic administration of butyrate, at physiologically relevant concentrations, dose-dependently decreases visceral sensitivity in healthy volunteers.